1. Field of the Invention
The present invention relates to a method for reconstructing immune function using pluripotent stem cells, and more particularly to a method for producing a human T cell, a pharmaceutical composition comprising the T cell produced by the method, and a method for cell-based immunotherapy using the method. The present invention also relates to an efficient method for producing a human CD8 single-positive cell (CD8 SP cell) having antigen specificity. The present invention also relates to a pharmaceutical composition comprising a human CD8 SP cell having antigen specificity which is produced by such a method, and to a method for cell-based immunotherapy using such a method.
2. Description of the Related Art
If supplementation or regeneration of immunocytes (immune cells) and others can be achieved in cases of decreased immune function resulting from various causes, then highly effective tools will be provided, for example, in ameliorating pathological conditions of and improving the effect of treatment of diseases. In particular, there is a strong need for supplementation of function of or regeneration of T lymphocytes and CD8 SP cells which are responsible for cellular immunity; however, no effective treatment methods have been established at present. This is largely because while immunological effects are characterized by their specificity, it is difficult to take good advantage of their specificity.
Along with recent rapid progress of genetic manipulation technology, attempts have been made to introduce antigen-specific T-cell receptor (TCR) genes into different types of lymphoid cells, thereby to supplement or regenerate specific immune reactions (Gattinoni L. et al., Nature Reviews Immunology, 2006, Vol. 6, pp. 383-393; and Morgan R. et al., Science, 2006, Vol. 314, pp. 126-129). These attempts used, for example, CD34 positive cells, which are a subset of myeloid progenitor cells, and naive T lymphocytes as cells for gene introduction. However, these types of cells suffer from many problems, such as a reduced capacity for ex vivo self-renewal, a low efficiency of gene introduction, difficulties in controlling their differentiation by gene introduction, and others.
Embryonic stem cells (ES cells) and artificial pluripotent stem cells (induced pluripotent stem cell, iPS cells) have recently been established from many animal species, including humans. These types of pluripotent stem cells would be the most useful source of cells for regenerative medicine because these cells are capable of differentiation into almost all of the organs by appropriate induction of their differentiation, with retaining their ability of actively dividing while maintaining their pluripotency. iPS cells, in particular, can be established from self-derived somatic cells, and therefore are not likely to cause ethical and social issues, in comparison with ES cells which are produced by destruction of embryos. Further, iPS cells, which are self-derived cell, make it possible to avoid rejection reactions, which are the biggest obstacle to regenerative medicine or transplantation therapy.
iPS cells can be established by reprogramming somatic cells in various methods. It has been a subject of great interest whether it is possible that since reprogrammed iPS cells carry, without any changes, the information of genes employed for the reprogramming, reprogramming can be also achieved in cells which have undergone gene rearrangement and terminal differentiation as in cells of the immune system, especially B- and T-lymphocytes. In such circumstances, there were reported the establishment of iPS cells from mouse B lymphocytes by Jaenisch et al. in 2008 (Hanna J. et al., Cell, 2008, Vol. 133, No. 2, pp. 250-264) and the establishment of iPS cells from mouse T lymphocytes by Yamanaka et al. in 2009 (Hong H. et al., Nature, 2009, Vol. 460, pp. 1132-1135). However, it has not been reported that iPS cells have been established from human T lymphocytes.
To realize immunotherapies using T lymphocytes, it is necessary that in addition to establishing iPS cells from human T lymphocytes, established iPS cells are induced to differentiate into functional T lymphocytes and CD8 SP cells, with retaining the TCR gene rearrangement pattern which is exhibited by the originating human T lymphocytes of the iPS cells. However, there have not been established such techniques yet.